Cardiac Allograft Rejection: Strategies for Success in the Face of Immune Challenges.

Heart transplantation for patients with end-stage heart failure refractory to medical therapy has remained definitive treatment with significant advances in posttransplant care. Despite improvement in postoperative morbidity and mortality, acute cellular rejection (ACR) and antibody-mediated rejection (AMR) remain substantial challenges that can lead to allograft failure and patient mortality. Immunosuppressive agents have been the mainstay of both prevention and treatment for ACR and AMR; however, many challenges exist with traditional therapies. There are a multitude of molecular pathways involved in mediating the humoral and cellular response to rejection, offering various targets for treatment. This review summarizes therapies used in the management of ACR and AMR as extrapolated from use in induction therapy and treatment of other solid-organ transplant rejection. Future studies focused on cardiac transplant recipients are needed to expand therapeutic options.

Evolution of concomitant use of veno-arterial extracorporeal membrane oxygenation support with Impella in cardiogenic shock: From percutaneous femoral Impella to axillary Impella 5.5.

BACKGROUND: Little is known about safety and efficacy of the use of Impella 5.5 compared to previous iterations in the setting of Impella with Veno-Arterial Extracorporeal Membrane Oxygenation Support as ECPELLA. METHODS: Consecutive patients who were treated by ECPELLA with surgically implanted axillary Impella 5.5 (N = 13) were compared with patients supported by ECPELLA with percutaneous femoral Impella CP or 2.5 (Control, N = 13). RESULTS: The total ECPELLA flow was higher in ECPELLA 5.5 group (6.9 vs. 5.4 L/min, p = 0.019). Actual hospital survival was higher than predicted and comparable in both groups (ECPELLA 5.5, 61.5% vs. Control, 53.8%, p = 0.691). Both total device complications (ECPELLA 5.5, 7.7% vs. Control, 46.1%, p = 0.021) and Impella-specific complications (ECPELLA 5.5, 0% vs. Control, 30.8%, p = 0.012) were significantly lower in the ECPELLA 5.5 group. CONCLUSIONS: Utilization of Impella 5.5 in the setting of ECPELLA provides greater hemodynamic support with a lower risk of complications compared to Impella CP or 2.5.

Ex Vivo Heart Perfusion for Cardiac Transplantation Allowing for Prolonged Perfusion Time and Extension of Distance Traveled for Procurement of Donor Hearts: An Initial Experience in the United States.

Scarcity of donor hearts continues to be a challenge for heart transplantation (HT). The recently Food and Drug Administration-approved Organ Care System (OCS; Heart, TransMedics) for ex vivo organ perfusion enables extension of ex situ intervals and thus may expand the donor pool. Because postapproval real-world outcomes of OCS in HT are lacking, we report our initial experience. Methods: We retrospectively reviewed consecutive patients who received HT at our institution in the post-Food and Drug Administration approval period from May 1 to October 15, 2022. Patients were divided into 2 groups: OCS versus conventional technique. Baseline characteristics and outcomes were compared. Results: A total of 21 patients received HT during this period, 8 using OCS and 13 conventional techniques. All hearts were from donation after brain death donors. The indication for OCS was an expected ischemic time of >4 h. Baseline characteristics in the 2 groups were comparable. The mean distance traveled for heart recovery was significantly higher in the OCS group (OCS, 845 ± 337, versus conventional, 186 ± 188 mi; P < 0.001), as was the mean total preservation time (6.5 ± 0.7 versus 2.5 ± 0.7 h; P < 0.001). The mean OCS time was 5.1 ± 0.7 h. In-hospital survival in the OCS group was 100% compared with 92.3% in the conventional group (P = 0.32). Primary graft dysfunction was similar in both groups (OCS 12.5% versus conventional 15.4%; P = 0.85). No patient in the OCS group required venoarterial extracorporeal membrane oxygenation support after transplant compared with 1 in the conventional group (0% versus 7.7%; P = 0.32). The mean intensive care unit length of stay after transplant was comparable. Conclusions: OCS allowed utilization of donors from extended distances that otherwise would not be considered because ischemic time would be prohibitive by conventional technique.

Simple technique of distal leg perfusion during heart transplant in patients with preoperative veno-arterial extracorporeal membrane oxygenation support.

Direct heart transplant from veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support is challenging. Continuation of postoperative VA-ECMO support may be required in the setting of primary graft dysfunction or severe vasoplegia. We describe a simple technique to perfuse the ipsilateral leg of an arterial ECMO cannula during heart transplant while the ECMO circuit is turned off but maintaining the arterial cannula and distal perfusion catheter in place. This technique minimizes the number of intraoperative procedures with a minimal risk of leg ischemia, and provides a smooth transition to postoperative VA-ECMO support if necessary.

Cannulation-related adverse events of peripheral veno-arterial extracorporeal membrane oxygenation support in heart transplantation: Axillary versus femoral artery cannulation.

BACKGROUND: In heart transplantation (HT), peripheral veno-arterial extracorporeal membranous oxygenation (VA-ECMO) is utilized preoperatively as a direct bridge to HT or postoperatively for primary graft dysfunction (PGD). Little is known about wound complications of an arterial VA-ECMO cannulation site which can be fatal. METHODS: From 2009 to 2021, outcomes of 80 HT recipients who were supported with peripheral VA-ECMO either preoperatively or postoperatively were compared based on the site of arterial cannulation: axillary (AX: N = 49) versus femoral artery (FA: N = 31). RESULTS: Patients in the AX group were older (AX: 59 years vs. 52 years, p = .006), and less likely to have extracorporeal cardiopulmonary resuscitation (0% vs. 12.9%, p = .040). Survival to discharge (AX, 81.6% vs. FA. 90.3%, p = .460), incidence of stroke (10.2% vs. 6.5%, p = .863), VA-ECMO cannulation-related bleeding (6.1% vs. 12.9%, p = .522), and arm or limb ischemia (0% vs. 3.2%, p = .816) were comparable. ECMO cannulation-related wound complications were lower in the AX group (AX, 4.1% vs. FA, 45.2%, p < .001) including the wound infections (2.0% vs. 32.3%, p < .001). In FA group, all organisms were gram-negative species. In univariate logistic regression analysis, AX cannulation was associated with less ECMO cannulation-related wound complications (Odds ratio, .23, p < .001). There was no difference between cutdown and percutaneous FA insertion regarding cannulation-related complications. CONCLUSIONS: Given the lower rate of wound complications and comparable hospital outcomes with femoral cannulation, axillary VA-ECMO may be an excellent option in HT candidates or recipients when possible.

Ecpella 5.5: An Evolution in the Management of Mechanical Circulatory Support.

There are several endovascular options for temporary mechanical circulatory support in patients with refractory cardiogenic shock. These devices are often utilized in tandem to provide maximal support, including the combination of venoarterial extracorporeal membrane oxygenation with the Impella device, termed ECPELLA. An underappreciated characteristic of mechanical circulatory support is whether they provide cardiac "replacement" and/or cardiac "assistance." Within this framework, we propose an evolution in the approach to ECPELLA utilizing the Impella 5.5, with a focus on the Impella 5.5 as the primary support device.

Role of MicroRNA in Heart Transplant.

The need for noninvasive biomarkers for diagnostic, prognostic, and therapeutic purposes is increasingly being recognized in the field of heart transplantation. MicroRNAs are a class of novel biomarkers that control gene expression and influence cellular functions, including differentiation, proliferation, and functional regulation of the immune system. They can be detected in the serum, plasma, and urine and may serve as early noninvasive biomarkers for various disease processes. Despite significant advances in heart transplantation, challenges remain in the short and long term with early graft injury and dysfunction, both cellular and antibody-mediated rejection, infections of varying types and severity, and cardiac allograft vasculopathy, which require an interventional approach for diagnosis and management. In this article, we review the current knowledge on the role of microRNAs in heart transplantation and its related complications and discuss their potential impact in future strategies to manage heart transplantation.